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The role of retinoid X receptors (RXRs) on negative thyroid
hormone response elements (nTREs) is not well understood. In this
report, we demonstrate that an orientation-specific monomeric thyroid
hormone receptor (T
Volume 270,
Number 23,
Issue of June 9, pp. 13899-13905, 1995
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
R) DNA-binding site mediates thyroid
hormone inhibition in the thyrotropin 
subunit gene (TSH-)
from human and murine species. Unlike positive TREs, addition of the
ligand 9-cis retinoic acid (9-cis RA) to cells transfected with a
TR 1 expression vector significantly reduces thyroid
hormone inhibition of the TSH- gene, indicating that endogenous
retinoid receptors antagonize TR function. Cotransfection
of an RXR-
but not a retinoic acid receptor- expression
vector further antagonizes thyroid hormone inhibition, but only in the
presence of 9-cis RA. Antagonism by RXR requires both an intact DNA-
and ligand-binding domain. Removal of monomeric TR binding
to the TSH- nTRE also requires both RXR domains. A model is
proposed whereby monomeric TR is removed from a nTRE by RXR
occupied by its ligand 9-cis RA. This is the first report of 9-cis
RA-dependent antagonism of thyroid hormone inhibition via negative
TREs.
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